Over 4,000 single gene disorders are inherited within families. Many of these disorders are quite common, but many others have been reported in less than 10 families. Hundreds of publications annually contribute to the identification of new disorders and to the further delineation of rare disorders. This source of information is of great value for clinical genetic diagnosis and genetic counseling. The purpose of this project is to assist in defining new genetic disorders and contributing to the further delineation of existing disorders. This often involves more detailed clinical studies of a patient than might be absolutely necessary on medical grounds. It frequently also involves clinical studies of family members who might not be seeking medical attention at the present time. In general, however, the additional studies would usually be desirable even on the grounds of in-depth clinical evaluation apart from research considerations. Patients eligible for this study would usually have been identified as good candidates for having novel or rare biochemical genetic disorders. This would usually be evaluated based on the clinical information and based on family history including issues such as multiple affected siblings and consanguinity. Subjects would be seen as inpatients or outpatients in the Clinical Research Center for performance of history and physical examination, if this was not already completed in the past. Laboratory studies of blood would usually include quantitative serum amino acid analysis, serum carnitine levels, various enzyme assays, and measurements of other biochemical metabolites depending upon the clinical circumstances.